Medroxyprogesterone Acetate

Drug Levels and Effects:




Summary of Use during Lactation:


Although nonhormonal methods are preferred during breastfeeding, progestin-only contraceptives such as depot medroxyprogesteroneacetate(DMPA) are considered the hormonal contraceptives of choice during all stages of lactation. Fair quality evidence indicates that DMPA does not adversely affect the composition of milk, the growth and development of the infant, or the milk supply.[1][2][3] Some evidence indicates that progestin-only contraceptives may offer some protection against bone mineral density loss during lactation, or at least not exacerbate it.[4][5][6]

The timing of initiation of DMPA is controversial.[7] The product labeling states that it should be started no sooner than 6 weeks postpartum, based on data submitted for product approval. Studies of fair quality seem to indicate that concerns about immediate adverse effects on the infants is unfounded; however, starting sooner theoretically could affect the newborn infant adversely because of slower metabolism of the drug than older infants. Of concern is that no data exist on the effects of progesterone on brain and liver development at this age. Administration sooner than 6 weeks postpartum could interfere with the exclusivity or duration of lactation. A systematic review of studies using early postpartum initiation of DMPA concluded that all of the studies were of low quality and inadequate to disprove the concern about DMPA's effects on milk production if given sooner than 6 weeks after delivery.[8]

Based on the available evidence, expert opinion in the United States holds that the advantages of using progestin-only contraceptive products generally outweigh the theoretical or proven risks before 4 weeks postpartum.[9] However, is prudent to give it no sooner than 3 days postpartum when lactation is established.[2][3]


Drug Levels:


Maternal Levels.

Seven women were given a single intramuscular dose of depot medroxyprogesteroneacetate150 mg 1 week after delivery. Peak milk levels occurred at varying times between days 8 to 28 after the injection, with most between 1 and 2 weeks. Peak levels ranged from 1.3 to 2.3 mcg/L. In 3 women, levels were measured 50 to 87 days after the dose and were still detectable in milk in the range of 0.54 to 0.98 mcg/L.[10]

Ten women received a single dose of depot medroxyprogesteroneacetate150 mg at 6 to 7 weeks postpartum. Breastmilk levels were measured weekly for 12 weeks. Average milk levels were highest at 1 week after injection at about 7.5 mcg/L and gradually fell to about 0.5 mcg/L at 12 weeks after the injection. The authors estimated that a breastfed infant would receive 1 to 13 mcg/day at 1 week after injection, 0.2 to 1.5 mcg/day 8 weeks after injection and up to 1 mcg/day at 12 weeks after injection.[11]

Infant Levels.

Thirteen male infants whose mothers received 150 mg of medroxyprogesteroneacetateintramuscularly at weeks 6 and 18 postpartum were breastfed. Complete 4-hour urine specimens were collected on 20 occasions during maternal treatment, including on the days after the injection known to have high maternal serum levels. No medroxyprogesterone or metabolites were detected by GC-MS assay (lower limit not specified) in the urine of the infants.[12]


Effects in Breastfed Infants:


In a nonrandomized study, 228 women chose depot medroxyprogesteroneacetateinjection every 3 months as a postpartum contraceptive starting in months 2 to 4 postpartum. Eighty-eight percent of the women breastfed their infants for at least 6 months. Infants were examined during the study and again at age 4.5 years. No adverse effects on infant growth and development were noted in the exposed infants.[13]

One follow-up study of 1215 children whose mothers received depot medroxyprogesterone during nursing reported a delayed appearance of pubic hair (reported by mothers) in pubescent girls, but not boys. No other effects on growth were observed after correction for socioeconomic status.[14]

A multicenter, nonrandomized study followed 541 infants whose mothers received depot medroxyprogesteroneacetateinjection 150 mg every 3 months for contraception during breastfeeding. No adverse effects on infant growth through the first year were found in comparison to standard measurements.[15][16]

Thirteen male breastfed infants whose mothers received 150 mg of medroxyprogesteroneacetateintramuscularly at weeks 6 and 18 postpartum were studied. No differences were found in serum levels of luteinizing hormone, follicle-stimulating hormone, unconjugated testosterone, or cortisol compared to those of a group of 9 control infants.[12]

In a nonrandomized study comparing 190 infants of women using depot medroxyprogesterone to those using a nonhormonal contraceptive or no contraception starting at about day 57 postpartum, no difference in infant growth rates were seen from birth to 6 months of age, regardless of whether the infant was fully or partially breastfed.[17]

In a retrospective cohort study of 270 infants whose mothers were given DMPA postpartum, no effect of DMPA on weight when adjusted for cofounders and no differences between groups in psychomotor development, milestones, health problems, infant height or physical examinations.[18]

A non-blinded, randomized study of exclusively breastfeeding women compared those who received an etonogestrel implant 24-48 hours after delivery (n = 20) to those who received a 150 mg depot medroxyprogesteroneacetateinjection at 6 weeks postpartum (n = 20). No difference in infant weight gain was noted between the two groups.[19]


Possible Effects on Lactation:


Galactorrhea has been reported in nonpregnant, nonlactating women using depot medroxyprogesteroneacetate(DMPA). In one case series, 3.6% of 360 adolescents who used depot medroxyprogesteroneacetateas a contraceptive for at least 6 months developed galactorrhea with normal prolactin levels.[20]

Numerous studies found that the use of intramuscular depot medroxyprogesteroneacetateas a contraceptive beginning at 7 days postpartum or later either has no negative effect or causes increases in the milk supply, duration of lactation or quality of breastmilk.[13][15][17][18][21][22][23][24][25][26][27] However, most of these were so seriously flawed that no valid conclusion can be drawn on the effect of early initiation on breastfeeding duration.[8]

Twenty-five women who were 6 weeks postpartum were given a single injection of 150 mg of depot medroxyprogesteroneacetate. Serum prolactin levels were compared to those of 25 women who used an IUD. All women breastfed their infants to about the same extent. Basal serum prolactin levels were similar between the groups at the beginning of the study. These levels slowly decreased in the IUD group, but increased in the medroxyprogesterone group. The differences were statistically significant at 6 weeks after the start of the study. Basal prolactin increases in the medroxyprogesterone were 14% over baseline and 59% over the IUD group at 6 weeks.[28]

Women (n = 80) were assigned randomly to receive intramuscular depot medroxyprogesteroneacetate(DMPA) 250 mg 1 to 2 days postpartum. Other women in the study (n = 616) were started on DMPA at 30 days postpartum. The median duration of lactation in both groups was longer in these women than the lactation duration following previous births.[29]

A nonrandomized, nonblinded study compared women who received either nonhormonal contraception (n = 56) or depot medroxyprogesteroneacetate(n = 47) 150 mg intramuscularly upon discharge from the hospital. No statistical differences were found in the breastfeeding rates or percentage of women exclusively breastfeeding between the 2 groups of women at 1, 4, 8, 12 or 16 weeks postpartum.[30]

In a nonrandomized, nonblinded study comparing women who were breastfeeding at discharge, 102 postpartum women received depot medroxyprogesteroneacetate(dosage not stated) in the early postpartum period (average 51.9 hours postpartum; range 6.25 to 132 hours), 181 received another progestin-only contraceptive and 138 used nonhormonal contraception. No differences in breastfeeding rates were seen at 2 and 6 weeks, but women receiving any hormonal contraceptive were breastfeeding at a lower rate (72.1% vs 77.6%) at 4 weeks postpartum. The authors concluded that progestin-only contraception initiated in the early postpartum period had no adverse effects on breastfeeding rates.[31]


Alternate Drugs to Consider:


Etonogestrel,Levonorgestrel,Norethindrone


References:


1. Truitt ST, Fraser AB, Grimes DA et al. Combined hormonal versus progestin-only contraception in lactation. Cochrane Database Syst Rev. 2003;2:CD003988 (updated 6 May 2008). PMID:12804497
2. Queenan JT. Contraception and breastfeeding. Clin Obstet Gynecol. 2004;47:734-9. PMID:15326435
3. Anon. FFPRHC Guidance (July 2004): Contraceptive choices for breastfeeding women. J Fam Plann Reprod Health Care. 2004;30:181-9. PMID:15222930
4. Caird LE, Reid-Thomas V, Hannan WJ et al. Oral progestogen-only contraception may protect against loss of bone mass in breast-feeding women. Clin Endocrinol (Oxf). 1994;41:739-45. PMID:7889609
5. Diaz S, Reyes MV, Zepeda A et al. Norplant(R) implants and progesterone vaginal rings do not affect maternal bone turnover and density during lactation and after weaning. Hum Reprod. 1999;14:2499-505. PMID:10527977
6. Costa ML, Cecatti JG, Krupa FG et al. Progestin-only contraception prevents bone loss in postpartum breastfeeding women. Contraception. 2012;85:374-80. 22036473 PMID:22036473
7. Rodriguez MI, Kaunitz AM. An evidence-based approach to postpartum use of depot medroxyprogesteroneacetatein breastfeeding women. Contraception. 2009;80:4-6 . PMID:19501209
8. Brownell EA, Fernandez ID, Howard CR et al. A systematic review of early postpartum medroxyprogesterone receipt and early breastfeeding cessation: Evaluating the methodological rigor of the evidence. Breastfeed Med. 2012;7:10-8 PMID:22085201
9. Farr S, Folger SG, Paulen M, Tepper N, Whiteman M, Zapata L et al. U S. medical eligibility criteria for contraceptive use, 2010: adapted from the World Health Organization medical eligibility criteria for contraceptive use, 4th edition. MMWR Recomm Rep. 2010;59 (RR-4):1-86. PMID:20559203
10. Saxena BN, Shrimanker K, Grudzinskas JG. Levels of contraceptive steroids in breast milk and plasma of lactating women. Contraception. 1977;16:605-13. PMID:606500
11. Koetsawang S, Nukulkarn P, Fotherby K et al. Transfer of contraceptive steroids in milk of women using long-acting gestagens. Contraception. 1982;25:321-31. PMID:6213373
12. Virutamasen P, Leepipatpaiboon S, Kriengsinyot R et al. Pharmacodynamic effects of depot-medroxyprogesteroneacetate(DMPA) administered to lactating women on their male infants. Contraception. 1996;54:153-7. PMID:8899256
13. Zacharias S, Aguilera E, Assenzo JR, Zanartu J. Effects of hormonal and nonhormonal contraceptives on lactation and incidence of pregnancy. Contraception. 1986;33:203-13. PMID:2941236
14. Pardthaisong T, Yenchit C, Gray R. The long-term growth and development of children exposed to Depo-Provera during pregnancy or lactation. Contraception. 1992;45:313-24. PMID:1387602
15. Anon. Progestogen-only contraceptives during lactation: I. Infant growth. World Health Organization Task force for Epidemiological Research on Reproductive Health; Special Programme of Research, Development and Research Training in Human Reproduction. Contraception. 1994;50:35-53. PMID:7924321
16. Anon. Progestogen-only contraceptives during lactation: II. Infant development. World Health Organization, Task Force for Epidemiological Research on Reproductive Health; Special Programme of Research, Development, and Research Training in Human Reproduction. Contraception. 1994;50:55-68. PMID:7924322
17. Diaz S, Zepeda A, Maturana X et al. Fertility regulation in nursing women IX. Contraceptive performance, duration of lactation, infant gowth, and bleeding patterns during use of progesterone vaginal rings, progestin-only pills, Norplant implants, and Copper T 380-A intrauterine devices. Contraception. 1997;56:223-32. PMID:9408703
18. Jimenez J, Ochoa M, Soler MP et al. Long-term follow-up of children breast-fed by mothers receiving depot-medroxyprogesteroneacetate. Contraception. 1984;30:523-33. PMID:6241560
19. Brito MB, Ferriani RA, Quintana SM et al. Safety of the etonogestrel-releasing implant during the immediate postpartum period: a pilot study. Contraception. 2009;80:519-26. PMID:19913145
20. Omar HA, Zakharia RM, Kanungo S et al. Incidence of galactorrhea in young women using depot-medroxyprogesteroneacetate. ScientificWorldJournal. 2006;6:538-41. PMID:16680366
21. Karim M, Ammar R, El Mahgoub S et al. Injected progestogen and lactation. Br Med J. 1971;1(742):200-3. PMID:5099971
22. Zanartu J, Aguilera E, Munoz G, Peliowski H. Effect of a long-acting contraceptive progestogen on lactation. Obstet Gynecol. 1976;47:174-6. PMID:943074
23. Toddywalla VS , Joshi L, Virkar K. Effect of contraceptive steroids on human lactation. Am J Obstet Gynecol. 1977;127:245-9. PMID:835620
24. Dahlberg K. Some effects of depo-medroxyprogesteroneacetate(DMPA): observations in the nursing infant and in the long-term user. Int J Gynaecol Obstet. 1982;20:43-8. PMID:6126406
25. Zacharias S, Aguilera E, Jimenez J et al. The effects of hormonal and non-hormonal contraceptives on human lactation and on the re-establishment of fertility. Int J Gynaecol Obstet. 1987;25 (Suppl):249-55. PMID:2892718
26. Anon. Effects of hormonal contraceptives on breast milk composition and infant growth. World Health Organization (WHO) Task Force on Oral Contraceptives. Stud Fam Plann. 1988;19:361-9. PMID:2906764
27. Baheiraei A, Ardsetani N, Ghazizadeh S. Effects of progestogen-only contraceptives on breast-feeding and infant growth. Int J Gynaecol Obstet. 2001;74:203-5. PMID:11502302
28. Ratchanon S, Taneepanichskul S. Depot medroxyprogesteroneacetateand basal serum prolactin levels in lactating women. Obstet Gynecol. 2000;96:926-8. PMID:11084179
29. Guiloff E, Ibarra-Polo A, Zanartu J et al. Effect of contraception on lactation. Am J Obstet Gynecol. 1974;118:42-5. PMID:4128673
30. Hannon PR, Duggan AK, Serwint JR et al. The influence of medroxyprogesterone on the duration of breast-feeding in mothers in an urban community. Arch Pediatr Adolesc Med. 1997;151:490-6. PMID:9158442
31. Halderman LD, Nelson AL. Impact of early postpartum administration of progestin-only hormonal contraceptives compared with nonhormonal contraceptives on short-term breast-feeding patterns. Am J Obstet Gynecol. 2002;186:1250-8. PMID:12066106



Substance Identification:




Substance Name:

MedroxyprogesteroneAcetate

CAS Registry Number:

71-58-9

Drug Class:


  • Contraceptive Agents, Female

  • Contraceptives, Oral, Synthetic

  • Hormones

  • Progesterone Congeners


  • Administrative Information:




    LactMed Record Number:


    415


    Last Revision Date:


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